76. Goodey NM, Herbert KG, Hall SM, Bagley
KC (2011) Prediction of residues involved in
inhibitor specificity in the dihydrofolate
reductase family. Biochim Biophys Acta 1814
(12):1870–1879
77. McKie JH, Douglas KT, Chan C, Roser SA,
Yates R, Read M, Hyde JE, Dascombe MJ,
Yuthavong Y, Sirawaraporn W (1998) Rational drug design approach for overcoming
drug resistance-application to pyrimethamine
resistance in malaria. J Med Chem 41
(9):1367–1370
78. Wilson T, Edeson JFB (1953) Treatment of
acute malaria with pyrimethamine. Br Med J
1:253–255
79. Cowman AF, Morry MJ, Biggs BA, Cross
GAM, Foote SJ (1988) Amino acid changes
linked to pyrimethamine resistance in the
dihydrofolate reductase-thymidylate synthase
gene of plasmodium falciparum. Proc Natl
Acad Sci U S A 85(23):9109–9113
80. Lee J, Goodey NM (2011) Catalytic contributions from remote regions of enzyme structure. Chem Rev 111(12):7595–7624
81. Agarwal PK, Billeter SR, Ravi Rajagopalan
PT, Benkovic SJ, Hammes-Schiffer S (2002)
Network of coupled promoting motions in
enzyme catalysis. Proc Natl Acad Sci U S A
99(5):2794–2799
82. Okondo M (2015) Effects of allosteric mutations on DHFR. Thesis-Montclair State
University
83. Mauldin RV, Lee AL (2010) Nuclear magnetic resonance study of the role of M42 in
the solution dynamics of Escherichia coli
dihydrofolate reductase. Biochemistry 49
(8):1606–1615
84. Rod TH, Radkiewicz JL, Brooks CL 3rd
(2003) Correlated motion and the effect of
distal mutations in dihydrofolate reductase.
Proc Natl Acad Sci U S A 100
(12):6980–6985
85. Rajagopalan PT, Lutz S, Benkovic SJ (2002)
Coupling interactions of distal residues
enhance DHFR catalysis-mutational effects
on hydride transfer rates. Biochemistry
41:12618–12628
86. Wang L, Goodey NM, Benkovic SJ, Kohen A
(2006) The role of enzyme dynamics and
tunnelling in catalysing hydride transfer: studies of distal mutants of dihydrofolate reductase. Philos Trans R Soc Lond Ser B Biol Sci
361(1472):1307–1315
87. Fan Y, Cembran A, Ma S, Gao J (2013) Connecting protein conformational dynamics
with catalytic function as illustrated in
dihydrofolate reductase. Biochemistry 52
(12):2036–2049
88. Boehr DD, Dyson HJ, Wright PE (2008)
Conformational relaxation following hydride
transfer plays a limiting role in dihydrofolate
reductase
catalysis.
Biochemistry
47
(35):9227–9233
89. Li L, Falzone CJ, Wright PE, Benkovic SJ
(1992) Functional role of a mobile loop of
Escherichia coli DHFR in transition-state stabilization. Biochemistry 31(34):7826–7833
90. Gekko K, Kunori Y, Takeuchi H, Ichihara S,
Kodama M (1994) Point mutations at
glycine-121 of E. coli DHFR-important
roles of a flexible loop in the stability and
function. J. Biochemist 116:34–41
91. Cameron CE, Benkovic SJ (1997) Evidence
for a functional role of the dynamics of
glycine-121 of E. coli DHFR obtained from
kinetic analysis of a site-directed mutant. Biochemistry 36:15792–15800
92. Venkitakrishnan
RP,
Zaborowski
E,
McElheny D, Benkovic SJ, Dyson HJ, Wright
PE (2004) Conformational changes in he
active site loops of dihydrofolate reductase
during the catalytic cycle. Biochemistry
43:16046
93. Boehr DD, Schnell JR, McElheny D, Bae SH,
Duggan BM, Benkovic SJ, Dyson HJ, Wright
PE (2013) A distal mutation perturbs
dynamic amino acid networks in dihydrofolate
reductase.
Biochemistry
52
(27):4605–4619
94. Mauldin RV, Sapienza PJ, Petit CM, Lee AL
(2012) Structure and dynamics of the G121V
dihydrofolate reductase mutant: lessons from
a transition-state inhibitor complex. PLoS
One 7(3):e33252
95. Miller GP, Benkovic SJ (1998) Deletion of a
highly motional residue affects formation of
the Michaelis complex for E. coli DHFR. Biochemistry 37:6327–6335
96. Miller GP, Wahnon DC, Benkovic SJ (2001)
Interloop contacts modulate ligand cycling
during catalysis by Escherichia coli dihydrofolate reductase. Biochemistry 40(4):867–875
97. Behiry EM, Luk LY, Matthews SM, Loveridge EJ, Allemann RK (2014) Role of the
occluded conformation in bacterial dihydrofolate
reductases.
Biochemistry
53
(29):4761–4768
98. Abdizadeh H, Tamer YT, Acar O, Toprak E,
Atilgan AR, Atilgan C (2017) Increased substrate affinity in the Escherichia coli L28R
dihydrofolate reductase mutant causes trimethoprim resistance. Phys Chem Phys 19
(18):11416–11428
218
Melanie Goldstein and Nina M. Goodey
KC (2011) Prediction of residues involved in
inhibitor specificity in the dihydrofolate
reductase family. Biochim Biophys Acta 1814
(12):1870–1879
77. McKie JH, Douglas KT, Chan C, Roser SA,
Yates R, Read M, Hyde JE, Dascombe MJ,
Yuthavong Y, Sirawaraporn W (1998) Rational drug design approach for overcoming
drug resistance-application to pyrimethamine
resistance in malaria. J Med Chem 41
(9):1367–1370
78. Wilson T, Edeson JFB (1953) Treatment of
acute malaria with pyrimethamine. Br Med J
1:253–255
79. Cowman AF, Morry MJ, Biggs BA, Cross
GAM, Foote SJ (1988) Amino acid changes
linked to pyrimethamine resistance in the
dihydrofolate reductase-thymidylate synthase
gene of plasmodium falciparum. Proc Natl
Acad Sci U S A 85(23):9109–9113
80. Lee J, Goodey NM (2011) Catalytic contributions from remote regions of enzyme structure. Chem Rev 111(12):7595–7624
81. Agarwal PK, Billeter SR, Ravi Rajagopalan
PT, Benkovic SJ, Hammes-Schiffer S (2002)
Network of coupled promoting motions in
enzyme catalysis. Proc Natl Acad Sci U S A
99(5):2794–2799
82. Okondo M (2015) Effects of allosteric mutations on DHFR. Thesis-Montclair State
University
83. Mauldin RV, Lee AL (2010) Nuclear magnetic resonance study of the role of M42 in
the solution dynamics of Escherichia coli
dihydrofolate reductase. Biochemistry 49
(8):1606–1615
84. Rod TH, Radkiewicz JL, Brooks CL 3rd
(2003) Correlated motion and the effect of
distal mutations in dihydrofolate reductase.
Proc Natl Acad Sci U S A 100
(12):6980–6985
85. Rajagopalan PT, Lutz S, Benkovic SJ (2002)
Coupling interactions of distal residues
enhance DHFR catalysis-mutational effects
on hydride transfer rates. Biochemistry
41:12618–12628
86. Wang L, Goodey NM, Benkovic SJ, Kohen A
(2006) The role of enzyme dynamics and
tunnelling in catalysing hydride transfer: studies of distal mutants of dihydrofolate reductase. Philos Trans R Soc Lond Ser B Biol Sci
361(1472):1307–1315
87. Fan Y, Cembran A, Ma S, Gao J (2013) Connecting protein conformational dynamics
with catalytic function as illustrated in
dihydrofolate reductase. Biochemistry 52
(12):2036–2049
88. Boehr DD, Dyson HJ, Wright PE (2008)
Conformational relaxation following hydride
transfer plays a limiting role in dihydrofolate
reductase
catalysis.
Biochemistry
47
(35):9227–9233
89. Li L, Falzone CJ, Wright PE, Benkovic SJ
(1992) Functional role of a mobile loop of
Escherichia coli DHFR in transition-state stabilization. Biochemistry 31(34):7826–7833
90. Gekko K, Kunori Y, Takeuchi H, Ichihara S,
Kodama M (1994) Point mutations at
glycine-121 of E. coli DHFR-important
roles of a flexible loop in the stability and
function. J. Biochemist 116:34–41
91. Cameron CE, Benkovic SJ (1997) Evidence
for a functional role of the dynamics of
glycine-121 of E. coli DHFR obtained from
kinetic analysis of a site-directed mutant. Biochemistry 36:15792–15800
92. Venkitakrishnan
RP,
Zaborowski
E,
McElheny D, Benkovic SJ, Dyson HJ, Wright
PE (2004) Conformational changes in he
active site loops of dihydrofolate reductase
during the catalytic cycle. Biochemistry
43:16046
93. Boehr DD, Schnell JR, McElheny D, Bae SH,
Duggan BM, Benkovic SJ, Dyson HJ, Wright
PE (2013) A distal mutation perturbs
dynamic amino acid networks in dihydrofolate
reductase.
Biochemistry
52
(27):4605–4619
94. Mauldin RV, Sapienza PJ, Petit CM, Lee AL
(2012) Structure and dynamics of the G121V
dihydrofolate reductase mutant: lessons from
a transition-state inhibitor complex. PLoS
One 7(3):e33252
95. Miller GP, Benkovic SJ (1998) Deletion of a
highly motional residue affects formation of
the Michaelis complex for E. coli DHFR. Biochemistry 37:6327–6335
96. Miller GP, Wahnon DC, Benkovic SJ (2001)
Interloop contacts modulate ligand cycling
during catalysis by Escherichia coli dihydrofolate reductase. Biochemistry 40(4):867–875
97. Behiry EM, Luk LY, Matthews SM, Loveridge EJ, Allemann RK (2014) Role of the
occluded conformation in bacterial dihydrofolate
reductases.
Biochemistry
53
(29):4761–4768
98. Abdizadeh H, Tamer YT, Acar O, Toprak E,
Atilgan AR, Atilgan C (2017) Increased substrate affinity in the Escherichia coli L28R
dihydrofolate reductase mutant causes trimethoprim resistance. Phys Chem Phys 19
(18):11416–11428
218
Melanie Goldstein and Nina M. Goodey